The effect of anesthetic drugs and techniques on cerebral metabolism and blood flow with particular attention given to either toxic or protective effects continues to be the major thrust of this proposal. If protection effects are suspected these will be tested in animal models of cerebral ischemia and cerebral hypoxia. Ongoing studies include those dealing with the possible protective effects of barbiturates, diphenylhydantoin, physostigmine and hypothermia. Animal models include those of complete cerebral ischemia in the dog, incomplete cerebral ischemia in primates (middle cerebral artery occlusion) and hypoxia in the mouse. Studies concerned with the effect of anesthetics on CSF rate of production and absorption are also in the planning stage. Because of recent reports that both hypercarbia and hypoxemia initially stimulate cerebral metabolism and increase oxygen consumption, we plan to repeat these studies in a dog model using the methodologies available to us. Finally because of an observed detrimental effect of prolonged hypothermia and rewarming, we plan studies to examine possible mechanisms of such a detrimental effect and means by which these can be avoided.